descriptionForkhead box (FOX) proteins are a family of transcription factors defined by a forkhead DNA-binding domain, which are involved in a range of functions. Of the FOXP protein subfamily, which includes FOXP1-4, FOXP1 and FOXP2 have been indicated in cognitive disorders (Bacon et al., 2012). Mutations in FOXP1 are associated with intellectual disability and may also cause language impairment as well as autistic features (OMIM 613670). FOXP2 mutations are known to cause a severe speech and language disorder (OMIM 602081); autistic features have been reported in some cases.

The FOXP1 gene (21 exons) spans ~635 kb of genomic DNA and is located on 3p14.1, 71 Mb from the p-telomere. The FOXP2 gene (18 exons) spans ~323 kb of genomic DNA and is located on 7q31.1, 114 Mb from the p-telomere. The P475-A1 probemix contains one probe for each exon of these genes and two probes for FOXP1 exons 3-7, and FOXP2 exons 3 and 4. In addition, 8 reference probes are included in this probemix, detecting several different autosomal chromosomal locations.

This SALSA® MLPA® probemix is designed to detect deletions/duplications of one or more sequences in the aforementioned gene(s) in a DNA sample. Heterozygous deletions of recognition sequences should give a 35-50% reduced relative peak height of the amplification product of that probe. Note that a mutation or polymorphism in the sequence detected by a probe can also cause a reduction in relative peak height, even when not located exactly on the ligation site! In addition, some probe signals are more sensitive to sample purity and small changes in experimental conditions. Therefore, deletions and duplications detected by MLPA should always be confirmed by other methods. Not all deletions and duplications detected by MLPA will be pathogenic; users should always verify the latest scientific literature when interpreting their findings. We have no information on what percentage of defects in these genes is caused by deletions/duplications of complete exons. Finally, note that most defects in this gene are expected to be small (point) mutations which will not be detected by this SALSA® MLPA® test.